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Syntaxin-4 is essential for IgE secretion by plasma cells
Institution:1. University Hospitals Leuven and KU Leuven, Leuven, Belgium;2. Thomas Jefferson University, Philadelphia, PA, USA;3. Novant Health Oncology Specialists, Winston-Salem, NC, USA;4. Western Hospital, Footscray, VIC, Australia;5. Emory University, Atlanta, GA, USA;6. UC Davis Comprehensive Cancer Center, Sacramento, CA, USA;7. Centre Hospitalier Universitaire de Liége Sart Tilman, Liège, Belgium;8. Sint Augustinus, Antwerpen, Belgium;9. Virginia Piper Cancer Institute, Minneapolis, MN, USA;10. Royal Women''s Hospital, Melbourne, VIC, Australia;11. Quintiles, San Diego, CA, USA;12. Amgen Inc., Thousand Oaks, CA, USA;13. H. Lee Moffitt Cancer Center, Tampa, FL, USA;1. Department of Pathology and Anatomical Sciences, State University of New York, Buffalo, 206 Farber Hall, 1300 University Blvd., University at Buffalo, NY 14214-3005, USA;2. Targacept Inc., 200 E 1st St #300, Winston-Salem, NC 27101-4165, USA;3. Department of Biochemistry and Neuroscience, Lake Erie College of Osteopathic Medicine, 1858 West Grandview Boulevard, Erie, PA 16509-1025, USA
Abstract:The humoral immune system provides a crucial first defense against the invasion of microbial pathogens via the secretion of antigen specific immunoglobulins (Ig). The secretion of Ig is carried out by terminally differentiated B-lymphocytes called plasma cells. Despite the key role of plasma cells in the immune response, the mechanisms by which they constitutively traffic large volumes of Ig out of the cell is poorly understood. The involvement of Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins in the regulation of protein trafficking from cells has been well documented. Syntaxin-4, a member of the Qa SNARE syntaxin family has been implicated in fusion events at the plasma membrane in a number of cells in the immune system. In this work we show that knock-down of syntaxin-4 in the multiple myeloma U266 human plasma cell line results in a loss of IgE secretion and accumulation of IgE within the cells. Furthermore, we show that IgE co-localises with syntaxin-4 in U266 plasma cells suggesting direct involvement in secretion at the plasma membrane. This study demonstrates that syntaxin-4 plays a critical role in the secretion of IgE from plasma cells and sheds some light on the mechanisms by which these cells constitutively traffic vesicles to the surface for secretion. An understanding of this machinery may be beneficial in identifying potential therapeutic targets in multiple myeloma and autoimmune disease where over-production of Ig leads to severe pathology in patients.
Keywords:Syntaxin-4  VAMP3  Plasma cells  IgE secretion  SNARE  Multiple myeloma
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